Shock causes alterations in cell function. The purpose of this proposal is to examine some of the mechanisms responsible for these alterations, specifically excitation secretion coupling and excitation contraction coupling. Shock causes changes in plasma hormone levels and the release or build up of toxic factors in the plasma. These extracellular mediators act on cell membranes which in turn cause changes in intracellular cyclic nucleotides and Ca ions which are also called second messengers. These second messengers in turn affect various cell function including protein synthesis and initiation of contraction in excitable cells. Using harvested shock plasma we will incubate this with monolayer cultures of adrenocortical cells to study defects in excitation secretion. Corticosterone Synthesis and alterations in cAMP, cGMP, and Ca ions fluxes will be measured and compared to control plasma. Similarly, monolayer cardiac myoblasts will be studied for defects in excitation-contraction coupling. Once defects have been identified therapeutic manipulations will be attempted.